Oxidative stress can be induced by both aerobic and resistance exercise (1,22,44), especially when the exercise is of high intensity (1,14). It is postulated that oxygen-containing free radicals such as the hydroxyl ion, superoxide, hydroperoxyl, and lipid peroxyl are generated after exercise. These increases are due to either the increased electron flux through the mitochondrial electron transport system in aerobic exercise or the ischemia-reperfusion-induced activation of the xanthine oxidase pathway in resistance exercise (4,14,22,44). Normally, the small percentage of electrons that escape the transport system are rendered inert by endogenous enzymatic and nonenzymatic antioxidants within the tissue (46). During exercise, however, when the production of the radicals exceeds the antioxidant capacity of the tissue, the radicals quickly react with cellular components (13). The consequence of excessive production of reactive intermediates such as protein carbonyls, malondialdehyde, or lipid hydroperoxides is interference of the normal biochemical pathways in the cells. This oxidant stress is associated with reduced contractile function, arrhythmias, and muscle fatigue (17,42,46) and has been implicated in pathologies such as diabetes, atherosclerosis, hypertension, and obesity (2,7,15,16,42).
Recent evidence has shown that obesity may predispose the individual to oxidative stress through several mechanisms (20,27,42,43). Obese individuals may increase muscular work from carrying excessive weight, and this can subsequently increased radical production via increased oxidative phosphorylation and electron leakage in the electron transport chain (1,46). A decreased antioxidant defense has been documented in obese populations such that there are lowered tissue levels of vitamins (β-carotene and vitamin C) (4,38), antioxidant enzymes (superoxide dismutase and glutathione peroxidase), and thiol-containing molecules such as glutathione (26,33) placing them at greater risk for free radical attack. Increased lipid targets such as cholesterol and triglycerides within plasma are available for oxidation in obese populations (18,21,43). Additionally, elevated leptin levels in obesity may stimulate intracellular production of free radicals such as hydrogen peroxide and the hydroxyl radical (2).
Although exercise can provide multiple health benefits to obese persons in the long term, acute intensive exercise can generate damaging oxidative stress that may exacerbate complications of obesity, such as diabetes and nephropathy (40). The shift toward pro-oxidation that occurs during activity may acutely increase microangiopathic processes and endothelium impairment via lipid peroxidation and glycosylation end-products and may place obese individuals at greater risk of physiological complications such as cardiac arrhythmias, fibrinolysis, and angina, and long-term complications such as development of atherosclerosis (16). Recent reports even suggest that exercise above 70–75% V̇O2max may increase the oxidation rate of LDL (45) and compromise endothelial function via increased usage of antioxidants and free radical formation (8), and this can be problematic considering the propensity for obese persons toward endothelial dysfunction and atherosclerosis (37). Acute resistance or aerobic exercise has independently been shown to increase oxidative stress in healthy, untrained, or trained persons (3,22) and in populations that are susceptible to oxidant stress such as the elderly (44), Type I diabetic patients (19), and heart failure patients (24). At present, there are no data regarding exercise-induced oxidative stress in the obese population.
Because several physiological variables may predispose the obese individual to oxidant stress, including increased oxygen usage for muscle metabolism, decreased antioxidant intake and status, and increased lipid level, and health risks are associated with oxidative stress in the obese (11), it is critical to understand how exercise affects oxidative stress status in obese persons. The purposes of this study were: 1) to compare oxidative stress levels (i.e., lipid peroxidation by-products) after acute resistance and aerobic exercise, and 2) determine whether obesity exacerbates oxidative stress in each mode of exercise.
Twenty-eight apparently healthy men and women volunteered as participants for this study. All participants had to meet the following criteria before enrollment in the study: 1) no participation in regular physical activity; 2) no chronic health problems or smoking; and 3) no history of cardiovascular, metabolic, or respiratory disease; and 4) had not consumed antioxidant supplements within the past 6 months. Participants attended a brief orientation meeting before data collection, and all participants read and signed a written informed consent statement consistent with university guidelines. All participants completed a Par-Q Health History questionnaire. The protocol of the study was approved by the Institutional Review Board for Studies Involving Human Participants at Stetson University and conforms to the guidelines involving the use of human participants as outlined by the American College of Sports Medicine (ACSM).
Participants were placed into one of two groups based on body mass index (BMI) and body fat percentage. Participants who were above 30% body fat and had a BMI above 30 kg·m−2 were placed into the “obese” group, and those who had body fat percentages and BMI values <25 kg·m−2 were placed into the “nonobese” group. Participants were age-matched for statistical comparison.
All participants visited the lab three times. All participants were acclimated to the use of the treadmill and the use of dumbbells. Correct execution of each exercise was supervised by the investigators. During visit 1, body fat analysis and resting heart rate (HR) and blood pressure (BP) were measured. Participants then completed one repetition maximums (1RM) on a series of seven dumbbell exercises; the 1RM were used to calculate exercise weight values at 60% and 80% of the 1RM for the resistance exercise session during visit 2. During visits 2 and 3, participants had their resting metabolic rate (RMR) measured, followed by a preexercise blood draw. The resistance exercise and aerobic exercise sessions were then completed respectively, followed by a postexercise metabolic rate and blood draw. The resistance exercise session was completed first in visit 2 to establish the HR responses necessary for the exercise target HR in the aerobic session for visit 3.
Three-day diet records were administered to each participant during visit 1. All participants were instructed to consume normal diets and to not consume any supplemental antioxidants during the testing period. All participants were provided a standard set of instructions on how to complete the record, along with pictorial guides for assistance in determining serving and portion sizes. Diet records were assessed by the same technician using Nutritionist Pro Software and were analyzed for macronutrient, antioxidant, and caloric intake.
Body weights were obtained to the nearest 0.1 kg using a double beam scale. Body mass index (BMI) values were calculated as body mass (kg)/ height (m)2. Body fat was predicted using the seven-site skinfold caliper method of Pollock et al. (28). All skinfold measures were performed by the same investigator.
After sitting quietly for 10 min, resting HR and BP were obtained in a seated position using standard auscultation procedures and a Trimline mercury sphygmomanometer (Pymah Co., Somerville, NJ). HR were obtained using HR monitors (Polar, Inc.). BP were recorded using the methods described by the American Heart Association (6,23). Mean arterial pressures (MAP) were calculated using the following formula: diastolic pressure + (pulse pressure/3).
After an overnight fast, participants in visits 2 and 3 relaxed for 30 min in a supine position. Expired gases were then collected for 10 min to determine RMR. Gases were collected through a low-resistance one-way valve (Hans Rudolph). Breath-by-breath analysis of expired gases was performed continuously throughout the test using a Max-1 Metabolic Cart (Physio-Dyne Software). The oxygen and carbon dioxide analyzers were calibrated before testing using a known gas mixture of 16.0% O2 and 5% CO2. Ventilatory responses (tidal volume and frequency of breathing) were measured with a pneumotachograph. Volume calibration was performed with a 3-L calibration syringe.
A blood draw was collected in a postabsorptive state (8–10 h). The RX session was conducted first. Participants then completed a resistance exercise (RX) session in which seven dumbbell exercises were completed (squat, chest press, lunge, rows, shoulder press, bicep curl, and tricep kick back). This exercise protocol was designed to simulate a moderate RX session that participants could perform at home or in an exercise facility. For each different exercise, participants were instructed to complete a warm-up set, a light set, and a heavy set (10 repetitions at 45% 1RM, 15 repetitions at 60% 1RM, and 8 repetitions at 80% 1RM, respectively). Each set was followed by a 1-min rest period. All exercises were supervised by a minimum of two investigators and assistants to ensure safety of the participant. Exercise HR measures were recorded from HR monitors (Polar, Inc.). HR were collected during each minute of the exercise test to obtain an average exercise HR during each exercise set and during the rest periods between each exercise. BP measurements were taken for every two exercises as a precautionary measure. Rating of perceived exertion (RPE) was obtained at the end of each exercise set using Borg’s RPE 6- to 20-point scale. On average, this RX session was completed within 38–44 min. As a measure of oxygen exposure to each participant, expired gases were collected continuously during each exercise session and were analyzed for oxygen uptake in absolute and relative values averaged in 5-s intervals. Immediately after the exercise, the participant returned to the supine position to collect expired gases, recovery HR, and BP. A blood sample was obtained immediately postexercise. Expired gases were collected for 10 min postexercise.
Seven days later, during the third visit to the lab, the participants repeated the preexercise metabolic measures as described above. The participants then completed an interval aerobic exercise (AX) session whose HR was matched to that of the RX session. Participants walked on a treadmill at a 10% grade and the speed was adjusted by the investigators to match the HR obtained during the RX session. The treadmill speed was adjusted so 2 min of exercise was at the target HR and 3 min was reduced intensity by decreasing the speed on the treadmill. Physiological measures were monitored as previously noted and the total time of the AX session matched that of the RX session.
Blood sampling, hematological markers.
Blood samples were obtained from a forearm vein of each participant in heparinized Vacutainer tubes before each exercise and immediately after each exercise. Blood was immediately centrifuged at 4000 rpm for 5 min to separate plasma from red blood cell pellets. Plasma samples were immediately frozen and stored at −70°C until analysis. Hematocrit values were assessed by centrifugation, and hemoglobin values were obtained using a commercial spectrophotometric kit with Drabkin’s reagent as the standard (Sigma, MO; Cat. no. 525-A). Blood glucose measures were assessed using a colorimetric, hexokinase-based enzymatic commercial kit (Sigma, no. 17–100P). All samples were assayed in duplicate.
Plasma lipid fractions were collected to determine the role of lipid type and content on oxidative stress levels in the plasma. Total cholesterol, HDL (HDL-C) and triglycerides were measured spectrophotometrically using commercial kits (Sigma Chemical Co, MO; procedures no. 401-500P and no. 336-10, respectively). HDL-C particles were separated from plasma samples by centrifugation in microtube separator columns and were analyzed colorimetrically using an aforementioned kit (no. 401-500P). LDL (LDL-C) were determined using the following formula: LDL-C = total cholesterol − HDL-C − (triglycerides/5).
Total antioxidant status (TAS).
As an estimate of the total antioxidant capacity of the plasma, a colorimetric commercial kit was used (Randox Laboratories, TAS Cat. no. NX2332). In brief, 2,2-azion-di-[3-ethylbenzenthiazoline sulfonate])(ABTS) was incubated with a peroxidase and hydrogen peroxide to produce a radical cation ABTS. The suppression of the ABTS radical in vitro was proportional to the antioxidant level in the plasma samples. Samples were read at 600 nm on a spectrophotometer. Samples were expressed in antioxidant capacity in millimoles per liter of plasma. All samples were performed in duplicate.
Lipid peroxidation measurements.
To determine the magnitude of oxidative stress in the plasma, two independent techniques were used to measure lipid peroxidation. Thiobarbituric reactive acid substances (TBARS) levels are a widely used nonspecific indicator of lipid peroxidation. TBARS were determined spectrophotometrically using the method previously described by Uchiyama and Mihara (39). The agent 1,1,3,3-tetraethoxypropane was used as the standard for this assay. Samples were performed in triplicate.
Lipid hydroperoxides were quantified using the colorimetric ferrous oxidation/xylenol orange technique previously reported, where cumene hydroperoxide was used as the standard for this assay (10). All samples were performed in triplicate.
All data are expressed in mean ± SEM. Data were analyzed using SPSS software (v. 10.1). Descriptive variables were analyzed using an unpaired Student’s t-test. A repeated measures, multivariate analysis of variance (MANOVA) was performed for both exercise bouts, with univariate tests to evaluate the specific effects on each dependent variable. The group membership was the between group factor (nonobese or obese) and time (pre- and postexercise) as the within group factor. When significant group by time interactions occurred, simple main effects were assessed using independent and paired t-tests. Levels of significance were set at 0.05. Pearson correlations were performed to determine associations between physiological measures and the change in lipid peroxidation. A Bonferroni test adjusted the level of significance to 0.005 for multiple correlations.
Table 1 reports characteristics for the experimental groups. Obese participants had significantly greater body masses, BMI values, percent body fat, and triglyceride levels compared with the nonobese group (P < 0.05). Obese participants had lower resting baseline V̇O2 (mL·kg −1·min−1) values compared with the nonobese (P < 0.05). All other variables were similar between groups.
Average dietary intakes are shown in Table 2. The obese group consumed more dietary fat compared with the nonobese group (a 10% difference in total energy intake comprised by fat; P < 0.05). There were no other significant differences in average caloric intake, daily macronutrient consumption or antioxidants, and vitamins E, C, and A.
The obese group had an elevated hematocrit level from pre- to post-RX (37.7 to 40.1%; P < 0.05) and elevated hemoglobin levels from pre-AX to post-AX time points (13.0 to 14.1 g·dL−1P < 0.05). After the AX session, the nonobese group had lower postexercise glucose levels compared with their preexercise values (0.57 mmol reduction; P < 0.05), whereas the obese group did not exhibit any change in glucose after either exercise. The post-AX glucose in the obese was higher than the nonobese, however (5.7 vs 4.8 mmol, respectively; P < 0.05). All other hemoglobin, hematocrit, and glucose responses were not different between groups or between exercise sessions.
The HR values were similar for both groups during the RX and AX sessions. The RPE values were consistently higher (P < 0.05) during each of the RX exercises compared with the corresponding RPE of the AX exercise in both groups. Systolic and diastolic BP tended to be higher in the obese group during the exercises, though these values did not reach significance. The MAP were not significantly different between groups at any exercise time point (P < 0.05).
Oxygen consumption and ventilation responses of both groups during RX and AX sessions are shown in Table 3. When expressed as V̇O2 consumption per unit fat free mass, the obese group had higher peak post-AX value compared with the RX session than the nonobese group (P < 0.05). All other exercise O2 consumption comparisons were not different between groups (P > 0.05). The obese participants had higher average V̇E than the nonobese group during the RX session, and higher peak V̇E values after both RX and AX compared with the nonobese group (P < 0.05).
The plasma lipid peroxidation values for both groups before and after exercise are shown in Figure 1, A and B. The baseline TBARS levels were not different between groups. Postexercise TBARS levels were elevated after the RX and AX, with the greater increases in the obese group compared with the nonobese (P < 0.05). Baseline PEROX levels were not statistically different before each type of exercise. PEROX levels increased in both groups after each exercise (P < 0.05), with the greater increase occurring in the obese group compared with the nonobese (P < 0.05). When the exercise-induced change in PEROX was standardized for average V̇O2 per kilograms of fat free mass during exercise, it was found that these lipid peroxidation values were still higher during RX in the obese group compared with the nonobese group (0.017 vs 0.047 nmol·kg−1 fat free mass, respectively, P < 0.05) but not post-AX (P > 0.05). Similarly, standardized TBARS levels were higher in the obese group compared with the nonobese post-RX (0.063 vs 0.013 nmol·kg−1 fat free mass, respectively) but not post-AX (P < 0.05).
Total antioxidant status (TAS).
The TAS values are shown in Figure 2. The nonobese group demonstrated a 17.8% increase in TAS from pre- to post-RX (P < 0.05), whereas a nonsignificant 8.6% decrease postexercise was obtained in the obese group. During the AX session, there was a nonsignificant 3.9% increase in TAS in the nonobese group. TAS was reduced, however, by 17.6% in the obese group after the AX (P < 0.05).
Pearson correlations were performed to determine the associations between the change in lipid peroxidation values and dietary, metabolic, and physiological factors that could contribute to oxidative stress. The significant relationships among the variables are shown in Table 4. In analysis of all participants, correlations existed among the change in PEROX prepost RX and vitamin C intake, peak V̇O2peak values achieved during the exercise sessions, peak V̇E, and average V̇E (P < 0.005). Post-AX lipid hydroperoxide levels were moderately correlated with plasma triglyceride levels and average exercise V̇E (P < 0.005). When separated by group, correlations existed between the change in PEROX and percent body fat, vitamin C intake, plasma triglycerides, and peak V̇E post-RX in the obese group (P < 0.005). After AX, change in PEROX was negatively correlated with vitamin A and C intake, and positively correlated with plasma triglycerides, V̇O2peak, and percent body fat in the obese group (P < 0.005).
In the present investigation obesity was found to exacerbate postexercise oxidative stress as shown by elevated lipid peroxidation levels. Despite the different and complex metabolic stressors imposed by RX and AX, both generated similar PEROX and TBARS levels. Postexercise oxidative stress in the obese may be related to several factors including V̇O2peak, during exercise, dietary antioxidant intake, and plasma fat content.
Exercise-induced oxidative stress.
In the present study, both RX and AX increased oxidative stress (e.g., elevated PEROX and TBARS). Similarly, previous reports have shown that levels of oxidative by-products increase after submaximal and maximal aerobic exercise (1,3,31,32,36,41,44), anaerobic exercise (sprint cycling) (9), and more recently, post-RX (isometric and dynamic) (1,22). The aforementioned studies have used a variety of exercise protocols and subject populations. Many of these studies have employed steady state bouts of aerobic exercise (stationary cycling or treadmill) (29,32,41), and only one has used heavy resistance exercise as the exercise stimulus (22). Some reports do not show elevated levels of biomarkers of lipid or protein oxidation (32,36,41), whereas others do (22,44). This discrepancy among protocols has been attributed to the intensity of the exercise not being sufficient to generate an oxidant challenge in the specific population tested (32).
Among all these studies, only one has compared the oxidative stress response to anaerobic and aerobic modes of exercise, and this was examined in healthy persons (1). The findings indicated oxidative modification of lipids and proteins after acute exhaustive bouts of static resistance and aerobic exercise (1). In the present study, we compared the oxidative stress levels after RX and moderate AX in obese persons. Even with exercise intensity differences between the work of Alessio et al. (1) and the current study, both AX and RX still elevated lipid peroxidation levels in all subjects. Despite different oxygen usage during AX and RX in the present study, oxidative stress occurred in each mode. This oxidative stress due to exercise is in part related to oxygen consumption (1). Similarly, Alessio et al. (1) reported higher V̇O2 values during exhaustive AX compared with isometric handgrip exercise. Even though differences existed in V̇O2 levels and recruitment of muscle mass in each type of exercise, oxidative stress occurred during both. Hence, sources for free radical formation and subsequent oxidative stress may exist in RX other than V̇O2, such as ischemia-reperfusion-mediated formation of superoxide (46), calcium-activated phospholipase activity (30), and leukocyte-derived free radicals (42).
In aerobic exercise, the elevated production of free radicals within the mitochondrial electron transport system is a likely mechanism for aerobic-exercise-induced lipid peroxidation (13,46). As electron flux increases within the electron transport system during exercise, the rate of electron leakage and formation of free radicals increases (46). Exercise-induced neutrophilia is another possible source of oxidant stress post-AX. Neutrophils generate superoxide radicals, reduce plasma vitamin C and uric acid, and create oxidative stress (29). Also, elevations in inflammatory cytokines such as tumor-necrosis factor-α (TNF-α) occur after AX (35). TNF-α initiates a rapid rise in endogenous oxidants as an essential step in postreceptor signal transduction (31).
In resistance exercise, elevated V̇O2 may contribute to free radical production. However, radical production may also be due to ischemia-reperfusion. Repeated bouts of ischemia and reperfusion in muscle can lead to formation of superoxide via activation of the xanthine/xanthine oxidase (XO) pathway (3,15,46). Superoxide formation is likely in RX, as muscular contractions at or above 40% of maximal voluntary contraction can produce transient ischemia in the muscle (5). Formation of superoxide in the XO pathway can cause inflammation, damage to cell membranes, oxidation of protein channels and transporters, and adhesion of leukocytes to the endothelium (17). Unaccustomed muscular work in our subjects may have lead to acute calcium imbalance within the muscle, an agonist for calcium-dependent phospholipases and phospholipid metabolism to harmful reactive aldehydes and alkanes by cyclooxygenase and lipoxygenase (30). These reactions can yield lipid peroxidation products. McBride et al. (22) found elevations in TBARS (~50%) after a heavy three-set circuit resistance exercise session in younger, weight-trained men. We observed similar TBARS elevations (~42%) after our RX session in our obese group, with a lower elevation in the nonobese group (~7%). The greater production of TBARS shown previously (22) is likely due to the comparatively greater resistance loads and exercise sets completed compared with those lifted by untrained subjects in the present study.
Obesity effects on oxidative stress in exercise.
Exacerbated exercise-induced lipid peroxidation in obesity may be due to several factors including an insufficient antioxidant defense. Plasma vitamins C and E and β-carotene levels are lower in obese adults (4,25). Despite comparable dietary intakes of antioxidants, obese persons have lower serum β-carotene and vitamin E than nonobese counterparts (38). Lower plasma antioxidants are accompanied by lower erythrocyte antioxidant enzyme activities such as superoxide dismutase and glutathione peroxidase (26). Lowered liver glutathione in rats was noted in obesity (33). Plasma lipids oxidize at a greater rate in obese subjects compared with nonobese and is due, in part, to lower anti-oxidant content in circulating lipids (27). A lowered anti-oxidant defense in obesity leaves the tissues susceptible to free radical attack especially in exercise, where free radicals are produced in excess.
The TAS measure represents the overall antioxidant capacity of the plasma from all possible antioxidants. The TAS values were higher in the nonobese group post-RX but not post-AX. This could suggest that the exercise mode taxes the circulating antioxidant pool differently or mobilizes antioxidants differently (3). It is unclear why this occurred in the present study, but could be related to differential mobilization of antioxidant components. Depending on the exercise intensity, blood-borne antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase may have increased their activities in response to the acute RX and AX (13,15). Alternatively, antioxidant mobilization or usage may differ in ischemia-reperfusion stress from RX versus a steady elevation in V̇O2 in AX. Evidence suggests that short-term maximal acute anaerobic exercise can increase plasma vitamin C levels while decreasing circulating α-tocopherol and β-carotene levels (9), whereas longer AX bouts can increase antioxidant enzyme activities and reduce glutathione (13). Our TAS data suggest that a greater oxidant production and antioxidant usage occurred during AX in the obese, as the obese had a lowered TAS post-AX compared with the nonobese.
Higher tissue lipid levels in the obese may provide a larger target for oxidative damage by free radicals (18,43). Elevated dietary fat intakes and plasma triglycerides were present in the obese compared with the nonobese group, resulting in positive correlations between these fat measures and exercise-induced change in PEROX. Our obese participants did not consume different levels of antioxidants than the nonobese group but did consume more dietary fats. Fat intake should be accompanied by increased antioxidant intake to reduce oxidative modification of the fat (21), and our obese participants may not have taken in antioxidant amounts necessary to prevent peroxidation reactions in the fat. With increased susceptibility to oxidation, elevated tissue lipids may be a major outlet for free radical attack in exercise in the obese, especially in exercise when more radicals are produced (27).
The metabolic load was greater for the obese versus the nonobese group in AX, despite matching cardiovascular stimuli (34). Although exercise increases oxidant production (12), oxidants were probably generated at a greater rate in the obese compared with the nonobese. To support this point, relative V̇O2 values were actually higher for the obese participants when compared with the nonobese during AX when expressed as a function of fat free mass. Therefore, oxygen uptake is an important aspect for AX oxidative stress but not with RX.
Although both the nonobese and obese groups had elevated lipid peroxidation levels postexercise, obesity exacerbated this response regardless of exercise modality. These data suggest that a combination of obesity-related factors including elevated body fat and triglyceride levels, antioxidant intake, and increased V̇O2 during exercise are involved in this process. However, it is suggested that oxygen uptake should be controlled and matched during exercise in obese and nonobese to ascertain whether obesity, independent of oxygen cost, results in greater oxidative stress in this population.
The authors wish to thank Dr. Cheryl Bourguignon (CSCAT) for her expertise and counsel with the statistical analysis. The authors also wish to thank Melissa Edwards and Jarrett Gardner for their technical assistance with the data collection.
The project described was supported by grant number 5-T32-AT00052 from the National Center for Complementary and Alternative Medicine (NCCAM), and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM or the National Institutes of Health.
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